At a time of growing interest in antibiotic development, a Wall Street bet on what some billed as a potential blockbuster appears to be going sour.
After regulators on Wednesday released a gloomy assessment of an experimental antibiotic developed by Cempra to combat community-acquired pneumonia, its stock sank as much as 58 percent. That’s because of a safety signal that was seen in another antibiotic called Ketek, which was linked to fatal liver problems years ago and later engulfed the US Food and Drug Administration in scandal.
In documents disclosed in advance of an expert panel meeting that will be held on Friday, FDA staff wrote that they found “a significant safety signal” for liver disease in Cempra’s solithromycin. Although Cempra designed its antibiotic to avoid the sort of side effects that were seen in patients treated with Ketek, agency medical reviewers noted that solithromycin is “structurally, highly related.”
This reference unnerved investors. Ketek, which remains available, was reviewed three times by the FDA before winning approval in 2004. Later, however, reports of serious liver injuries emerged, although the agency was accused of failing to act on information that the manufacturer, a company bought by Sanofi, submitted fraudulent study data. Congressional probes ensued and one doctor later went to jail.
For this reason, investors were rattled by the FDA assessment.
“The parallels FDA makes between the liver injury that plagued Ketek and the risk for solithromycin is just too great to be ignored by panelists on Friday,” wrote Baird analyst Brian Skorney in an investor note. “Even if approved with a risk mitigation strategy, sales limited to the Ketek market are unlikely to justify the cost of sales efforts, especially when competing with big pharma.”
“Although there are numerous infectious disease docs here who will likely support that [the antibiotic] hits non-inferiority, we doubt matching generic moxifloxacin [in clinical trials] is strong enough in the face of a suspect liver safety profile to get support for anything but the most restricted label,” he added.
Not everyone took a dim view, however, noting that the FDA found the antibiotic to be effective and the Cempra trials did not indicate evidence of acute liver damage.
“We are not at all surprised by the conservative, glass half-empty tone of the (FDA briefing) documents,” wrote Cowen analyst Ritu Baral in her own investor note. “We think the FDA panel will vote for approval, but with a sizable post-marketing safety commitment… We think the viability of the clinical package remains intact.”
The development follows weeks in which Cempra stock was already sliding. The decline, in fact, accelerated further five days ago after the company disclosed that FDA officials indicated production gaffes at Wockhardt, the contract manufacturer used to make the antibiotic, could be problematic. Cempra has arranged for another manufacturer, but trial data relies on product made by Wockhardt.
Other issues, though, have rumbled in the background, such as the Cempra marketing plan. Cempra chief executive Prabhavathi Fernandes wants to sell the antibiotic, which was developed in both oral and intravenous versions, at a lower price than other antibiotics in order to gain market share and not limit usage to hospitals for the toughest-to-treat patients. Skorney calls the strategy “questionable.”
For this reason, there has been investor hope that Cempra would, indeed, reach a broader market and eventually become a blockbuster, even though there is greater need for antibiotics that can fight superbugs that are contracted in hospitals.
“Antibiotic R&D isn’t easy,” said Kevin Outterson, a law professor at Boston University who heads Carb-X, a recently formed public-private partnership created to back biotech start-ups looking to develop antibiotics. “We do need some success stories in this area and, right now, this is not one of them.”
A spokeswoman for Cempra noted that the company is conducting a pediatric trial with backing from BARDA, the division of the US Department of Health and Human Services that is also providing funds Carb-X. The suggestion is that the Barda would not proceed with testing the Cembra antibiotic if it was aware of a safety concern.